Glucagon-like peptide (7-36) amide (GLP-1) is a hormone produced in the L cells of the small bowel and proximal colon.There is an increase in its release into the blood stream in response to food ingestion. It belongs to a class of peptides, known as incretins, which modulate insulin release from beta cells in the presence of glucose. It is the most potent of all th known incretins. Acute studies of GLP-1 have shown that it can synergize with glucose in stimulating insulin secretion both in vivo and in vitro and is one of the factors which maintains normal glucose tolerance, especially in the fed state. First, we studied the effects of long-term exposure of RIN 1046-38 cells, an insulin secreting cell line, to GLP-1 and the mechanisms by which GLP-1 synergizes with glucose in stimulating insulin secretion.We did further studies to investigate the effects of GLP-1 on beta cells. While GLP-1 has been accepted to increase insulin release after eating, it is still present in the fasting state in the serum at half the concentrations of the postprandial state. One of the earliest abnormalities in diabetes is a gradual rise in fasting sugar. A similar phenomenon of a gradual rise in blood sugar occurs in aging, with some people going on to develop diabetes. Insulin and glucagon primarily regulate fasting glucose. Under physiological conditions, when blood glucose is low, insulin levels are low and glucagon rises so that the liver can produce glucose. Therefore, we wished to elucidate if GLP-1 is also a factor in maintaining normal glucose tolerance in the fasted state. We found that when GLP-1 was inhibited in the fasting state in rats that blood glucose levels increased. This was because glucagon levels also increased, causing an increase in hepatic glucose output. Essentially a fasting animal can be made temporarily diabetic with GLP-1 inhibition.